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. Author manuscript; available in PMC: 2019 Apr 10.
Published in final edited form as: J Control Release. 2018 Feb 10;275:229–241. doi: 10.1016/j.jconrel.2018.02.003

Figure 2. Schematic representation of the differential absorption and disposition pathways of ARVs associated to DcNPs in TLC-ART101, free, or in a stationary depot in the SC or IM space.

Figure 2

In the SC space, ARV combinations (e.g., lopinavir [LPV], ritonavir [RTV], and tenofovir [TFV]) associated to drug combination nanoparticles (DcNPs) and referred to as “TLC-ART101,” are too large to enter blood capillaries, and thus preferentially enter lymph capillaries. While free ARVs in the SC space can enter lymph capillaries initially due to a strong concentration gradient driving drug out of the SC space, free ARVs are not able to be retained in the lymphatics and can easily diffuse back into the SC space as the diffusion gradient reverses direction over time. Overall, free ARVs preferentially enter the blood from the SC space, largely due to the 100-500-fold faster blood flow via capillaries than lymph flow. A stationary SC or intramuscular (IM) depot that provides a sustained release reservoir of free drug would follow the same principles for free drug and thus would also be predominantly absorbed directly into the blood. Once in lymphatic capillaries, TLC-ART101 particles would undergo first-pass distribution throughout the lymphatic system before entering the systemic blood circulation. In contrast, free drug that mostly enters the systemic circulation would undergo distribution, metabolism, and excretion mechanisms characteristic to the free drug molecule.